Primecuts – This Week in the Journals

February 22, 2012

By Aviva Regev

Faculty Peer Reviewed

In honor of President’s day, we’ll start this week’s Primecuts with a look towards Washington, where healthcare issues have made big news in the last week. Religious groups cried foul at President Obama’s new plan requiring most health plans to include free coverage for contraceptives and sterilization procedures, claiming the government was usurping their right to religious freedom in mandating they pay for services which violate their belief systems. The President, seemingly surprised by the uproar, came up with a compromise whereby the insurance companies, not the religious institutions themselves, would be responsible for the cost [1]. This has not appeased anyone, as the religious groups claim that the cost that rests on insurers will be passed back to the employers paying for the policies, and thus the “compromise” is essentially the same as the original plan. And thus the debate continues. Who doesn’t love a little election year rabble-rousing?

Since we can’t forget Valentine’s Day, let’s move on to matters of the heart. In NEJM this week, researchers shed light on a cause of idiopathic dilated cardiomyopathy [2]. Titin, the largest human protein and a key building block of sarcomeres, has long been a suspect but had not been previously analyzed extensively due to its enormous size. Now, thanks to next-generation sequencing, the massive TTN gene has been evaluated and found guilty, at least in a certain number of cases. Truncating mutations of TTN were found in about 25% of patients with familial idiopathic dilated cardiomyopathy and 18% of sporadic cases. The mutations were far more frequent in patients with dilated cardiomyopathy compared to those with hypertrophic cardiomyopathy or controls (p= 3×10-16 and 9×10-14, respectively). In families with these mutations, the penetrance was 95% in those over 40 years of age. Interestingly, the clinical manifestations, morbidity, and mortality were similar in dilated cardiomyopathy patients with and without TTN mutations, but among those with the mutation men suffered serious events such as transplantation, LVAD implantation, and death much earlier than women with the same mutation (56 vs. 68 years, p=4×10-5). Hopefully, recognition of these gene mutations will allow carriers to receive earlier diagnosis and intervention.

Before you reach for that heart-shaped box of chocolates, take a look at the new guidelines for management of type 2 diabetes published in the Annals of Internal Medicine this week [3]. After reviewing 44 years of literature, the authors came up with three recommendations which, thankfully, most clinicians are likely already following. First, in patients with type 2 diabetes who are not well controlled with diet, exercise, and weight loss, an oral hypoglycemic agent should be initiated. The second recommendation is that the initial treatment should be metformin monotherapy, and finally, if metformin alone does not control sugar levels, a second oral agent should be added. The authors offer no specific recommendations for the drug to use as second-line, though the authors do mention that generic sulfonylureas are the cheapest option, albeit with a worse side-effect profile than others.

Has too much smooching with your sweetie left you with a case of the sniffles? If you’ve come down with the flu, you may have your CD4+ T-cells to blame. While neutralizing antibodies play a role in influenza defense, we all know that strains change year-to-year and sometimes the medley in the vaccine just doesn’t hit the spot. New research in Nature Medicine [4] highlights the role of CD4+ cells in defense against novel flu strains. In healthy subjects with no antibodies to the test strains (H3N2 or H1N1), those with pre-existing T cells that responded to core viral proteins such as nucleoprotein and matrix proteins had milder infections. The presence of these preexisting CD4+ cells is very common, with 79% of the H3N2 group and 100% of the H1N1 group displaying a T cell response. The level of these T cells was inversely correlated with duration of symptoms in the group infected with H3N2 (r= -0.574, p=0.03) and also with virus shedding (r= -0.6087, p=0.0209). The level of pre-existing CD8+ cells did not have these effects. This introduces the possibility of harnessing this cytotoxic T cell response to make vaccines that may protect against a wider variety of seasonal influenza strains, as well as dreaded pandemic strains. The research also begs the question of who in their right mind would sign up to be infected with the flu, even if it is in the interest of the greater good!

Now, some scary news for city-dwellers: all that air pollution is not just bad for your lungs. In the Archives of Internal Medicine [5] this week, a study of 1700 stroke patients found a significant association between the rate of ischemic stroke and the air quality over a 24-hour period, as rated by the US Environmental Protection Agency’s Air Quality Index. The odds ratio of stroke onset following a moderate air quality period was 1.34 (p<0.001) compared with a good period. This increased risk was greatest in the first 12-14 hours after exposure to fine particulate matter, and was most associated with traffic-related pollution. Also in the Archives [6], long-term exposure to particulate matter at levels that are fairly common in the United States may contribute to cognitive decline in older women. A 10-?g/m3 increase in exposure over the long term is “cognitively equivalent to aging by approximately 2 years.” That is not insignificant, considering that the moderate air quality range spans 15-40?g/m3 and is considered an “acceptable” level of exposure.

For those of you still reading, we’ll come full circle and wrap up this week’s novella with some political food for thought: is a satisfied patient a healthy patient? A study in Archives [7] shows that higher “patient satisfaction” is associated with greater spending and a higher mortality rate. Read the article and a commentary from the Los Angeles Times [8], and tell us what you think.

One Response to Primecuts – This Week in the Journals

cathy carron md on February 22, 2012 at 3:06 pm

What a great little article you wrote. I only say ‘little’ because I read it while powering through my mini lunch break (of 15 mnutes).Well written, interesting and full of information. And an easy read!
What more could a harried Internist wish for? Well…

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